Triethylamine → HCID 67850543, compound

HRID 580965Notes

Reaction equation

HRID 580965 reaction equation
[C:1]([C:3]1([OH:11])[CH:8]2[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]2)[CH2:4]1)#[CH:2].Br[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][O:22][CH3:23])=[C:15]([Cl:24])[CH:14]=1.C(N(CC)CC)C>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I.CN(C)C=O>[Cl:24][C:15]1[CH:14]=[C:13]([C:2]#[C:1][C:3]2([OH:11])[CH:8]3[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]3)[CH2:4]2)[CH:18]=[CH:17][C:16]=1[O:19][CH2:20][CH2:21][O:22][CH3:23]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 36135173-Ethynyl-1-azabicyclo[2.2.2]octan-3-olHCID 57061342HCID 57061342, compound

Product 1

HCID 67850543HCID 67850543, compoundYield 51.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3-ethynyl-3-hydroxyquinuclidine (453 mg), methoxyethyl 4-bromo-2-chlorophenyl ether (0.97 g), bis(triphenylphosphine)palladium (II) chloride (105 mg), copper (I) iodide (55 mg), triethylamine (5 ml) and dimethylformamide (10 ml) was stirred at 70° C. under an atmosphere of argon for 2 hours. The triethylamine and dimethylformamide were removed by evaporation. The residue was purified by flash column chromatography on silica gel (Merck Art. No. 9385) using a mixture of 10% methanol in dichloromethane containing 1% ammonia (density, 0.880 g/cm3) as eluent. The residue was crystallised from acetonitrile to give 3-[2-(3-chloro-4-(2-methoxyethoxy)phenyl)ethynyl]quinuclidin-3-ol (0.52 g) as a colourless solid, m.p. 138-139° C.; microanalysis, found: C, 64.1; H, 6.7; N, 4.1%; C18H22ClNO3 requires: C, 63.9; H, 6.6; N, 4.1%; NMR ([CD3 ]2SO): 7.5(1H,d), 7.3(1H,d of d), 7.1(1H,d), 5.5(1H,s), 4.2(2H,m), 3.7(2H,m), 3.3(3H,s), 2.8(2H,m), 2.7(4H,m), 2-1.8(3H,m), 1.6(1H,m) and 1.3(1H,m); m/z 336(M+H).

Workup

  1. customThe triethylamine and dimethylformamide were removed by evaporation
  2. customThe residue was purified by flash column chromatography on silica gel (Merck Art
  3. additiona mixture of 10% methanol in dichloromethane containing 1% ammonia (density, 0.880 g/cm3) as eluent
  4. customThe residue was crystallised from acetonitrile

Sources & evidence

ORD record
ord-c2c19284c9134c2f800acdce198b564e
Source dataset
uspto-grants-1999_07
Patent number
US05919793

Reaction notes

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